Impact of independent multidisciplinary work on the survival rate of stage 3 and 4 nasopharyngeal cancer in Indonesia: a retrospective cohort study

Abstract

Background:

The utilization of a multidisciplinary team (MDT) strategy is a beneficial approach in integrating the knowledge and proficiencies of various fields to produce thorough and advantageous cancer treatment plans for patients. Nevertheless, MDT has yet to be widely adopted in Indonesia. In this study, the authors examined an early form of MDT in Indonesia that does not involve dedicated meetings, referred as independent multidisciplinary work (IMW). The objective is to investigate the differences in survival rates of nasopharyngeal cancer (NPC) patients who underwent treatment with and without IMW.

Materials and methods:

This study has a retrospective cohort design. Data were collected from the medical records of newly diagnosed stage 3 and 4 NPC patients between 2016 and 2018. The subjects were divided into two groups: the IMW group and the non-IMW group. The primary end point of the study is overall survival rate between the two groups. Kaplan–Meier survival analysis, log-rank test, and cox proportional hazard analysis were used for statistical analysis.

Results:

This study included a total of 124 patients with NPC, 81 patients in the IMW group and 43 patients in the non-IMW group. At the end of the 36-month follow-up period, the median survival of the IMW group was not reached, while in the non-IMW, it was 12 months [95% confidence intervals (95% CI), 8.78–15.22], hazard ratio (HR): 0.47 (95% CI, 0.28–0.78; P<0.01). The 1-year survival rate was 66.7% in the IMW group versus 46.5% in the non-IMW group (HR=0.7, 95% CI 0.49–0.99; P=0.03); the 2-year survival rate was 40.7% in the IMW group versus 16.3% in the non-IMW group (HR=0.4, 95% CI 0.19–0.83; P<0.01). Daniel Rizky, Vina Yunarvika, and Yasjudan Rastrama Putra, these authors contributed equally to this work. In the multivariate analysis, the IMW approach, ECOG (The Eastern Cooperative Oncology Group) status, distant metastasis, and treatment approach were significantly associated with survival outcome.

Conclusion:

The use of IMW approach in the treatment of NPC was associated with a better survival outcome compared to non-IMW treatment.

Introduction

Highlights

• In this retrospective cohort study, we investigated an early form of multidisciplinary team cancer treatment approach called independent multidisciplinary work (IMW) in Indonesia, which involves mutual consultation rather than dedicated meetings.

• The aim of this study is to compare the overall survival outcomes of patients with nasopharyngeal cancer (NPC) who received the IMW approach versus those who did not.

• A total of 124 stage 3 and 4 NPC patients were analyzed, with 81 patients in the IMW group and 43 patients in the non-IMW group.

• At the end of the 36-month follow-up period, the median survival for the IMW group was not reached, while it was 12 months (95% CI, 8.78–15.22) for the non-IMW group, hazard ratio (HR): 0.47 (95% CI, 0.28–0.78; P<0.01).

• The IMW approach was associated with better survival outcomes compared to non-IMW treatment in the NPC patients.

The global mortality rate for nasopharyngeal carcinoma (NPC) reaches 0.7 per 100 000 (1 per 100 000 in men and 0.4 per 100 000 in women). The five countries with the highest mortality rates from NPC in Asia are China (21 300), Indonesia (7391), Vietnam (2885), India (2836), and Thailand (1114) per 100 000 population¹. The incidence of NPC in Indonesia is 19.6 per 100 000 population, with a mortality rate of 4.5 per 100 000 population². The NPC overall survival (OS) rates for all stages range from 31 to 94.3% over a 5-year period^3,4. A Chinese study investigated locally advanced cases treated with either concurrent chemoradiotherapy or induction chemotherapy-concurrent chemoradiotherapy, revealing respective 5-year OS rates of 74.8% and 83.2%⁵. In Malaysia, another endemic Asian country, the 3-year OS rates were 94.3% for stage II, 80% for stage III, and 79.8% for stage IV^3,6. A recent study conducted by Hutajulu et al. projected the OS of NPC patients in Yogyakarta, Indonesia, to be ~35%, which is comparatively lower than the rates observed in non-endemic countries such as Slovenia, where a 5-year DFS (disease free survival) of 59% and an OS of 49.7% were reported^4,7.

As in other cancer types, the survival of NPC depends on how patient care is delivered. The complexity of cancer care highlights the importance and the need for the involvement of a multidisciplinary team (MDT). An MDT is an integrated team of healthcare professionals providing care by considering various relevant therapeutic options and individual treatment plans in a collaborative, integrated, comprehensive, effective, and efficient manner. Oncology MDT is important in oncology management and is an excellent tool for combining the expertise and skills from multiple disciplines to develop optimal treatment plans for cancer patients^8–10.

Studies have shown that MDT decisions lead to the revision of cancer diagnosis and treatment plans in new cancer cases and better adherence to evidence-based guidelines. MDT can improve diagnostic, staging, and survival, as well as reduce treatment time^11–15. The symptoms experienced by patients, therapeutic side effects, and physical and psychological impact may vary depending on the location of the cancer and the treatment plan. The integration of various professionals is believed to enhance patient management, as opposed to the traditional approach of a single physician providing global medical care. Conducting a pre-treatment MDT meeting is crucial to develop a more appropriate therapy plan. This meeting should include patients who are newly diagnosed or who have experienced a recurrence during follow-up or a change in treatment^10,14,16. The European Society for Medical Oncology (ESMO) recommends MDT discussions as the optimal approach for the management of NPC¹⁷.

Hospitals with sufficient facilities and human resources are considered capable of implementing MDT in cancer management. However, MDT has not yet become a common practice in Indonesia, and only a few hospitals have incorporated MDT into their services. In this study, we examined an early form of MDT in Indonesia that does not involve dedicated meetings, but rather mutual consultation, which we referred to as independent multidisciplinary work (IMW). We acknowledge that MDT is the most appropriate form of cancer management. To the best of our knowledge, there have been no studies in Indonesia that compare the survival outcomes of NPC patients treated with a multidisciplinary approach at two cancer centers simultaneously^18–21. This study aims to compare the OS outcomes of NPC patients who received IMW-based approach versus those who did not.

Materials and methods

Study design

This is a retrospective cohort study conducted in two national referral hospitals on the island of Java, Indonesia: the general hospital has adopted IMW for cancer care (IMW implemented hospital) and the one who has not (non-IMW implemented hospital).

Sample population

Data were extracted from the medical records according to the following selection criteria: (1) all stage 3 and 4 newly diagnosed NPC patients treated from 2016 to 2018 at the IMW implemented and non-IMW implemented hospitals; and (2) availability of information regarding WHO histopathology, distant metastasis status, and treatment approach. Data were collected from May 2021 to December 2022. Patients with missing data and a history of induction therapy or subsequent lines of therapy were excluded from the study.

The tumors were classified using the 2010 AJCC (American Joint Committee on Cancer) 7th and UICC (Union Internationale Centre le Cancer) criteria. This system accounts for the size of the tumor (T), the number, size, and location of the cervical lymph nodes (N), and the presence or absence of distant metastasis (M), and patients were treated accordingly. Nasopharyngeal cancer (NPC) is classified histologically according to the World Health Organization (WHO) criteria and subdivided into three categories: keratinizing squamous cell carcinoma (WHO type 1), non-keratinizing squamous cell carcinoma (WHO type 2), and undifferentiated or poorly differentiated carcinoma, including lymphoepithelioma and anaplastic variants (WHO type 3)^13,14.

Patients with IMW approach were collected from the hospital that has implemented an IMW approach for NPC treatment since 2008. Newly diagnosed patients and evaluations are discussed through consultations, without the need for specific meetings, among medical oncologists, ENT specialists, radiation oncologists, radiologists, pathologists, and other relevant specialists. This approach is referred to as independent multidisciplinary work (IMW). This IMW team consists of Ear, Nose, and Throat (ENT) specialists who performed diagnosis and local surgery, a medical oncologist who performed systemic treatment, a radiation oncologist, a pathologist, a radiologist, and oncology dedicated nurses. Other specialists may include oncology surgeons, other surgeons, neurologists, nutritionists, and physiotherapists whenever needed.

In the non-IMW implemented hospital, no specific meetings applied. Instead, the ENT specialist performed surgical procedures and systemic treatment, while radiation oncologists provided radiotherapy in most of the patients.

Main outcome of the study

The primary outcome of this study was the survival rates of patients with NPC who received treatment with IMW versus those who did not. The study aimed to determine if there were any significant differences in OS between the two groups after a 36-month follow-up period.

Data analysis

Data were collected from medical records, including age, sex, initial complaint, body mass index (BMI), comorbidities, The Eastern Cooperative Oncology Group (ECOG) performance status, clinical stage, WHO histopathology, distant metastasis, and therapeutic regimen result. The survival status of the samples was collected from the medical record. For those without information from the medical record, the patient or family was then contacted by the researcher to identify whether the patient is alive or has passed away.

Data were analyzed using SPSS Statistics software version v.21 (IBM Corp, Armonk, New York, USA). Data collected during the study are presented as mean, standard deviation, range, and percentages. Survival analysis was conducted using the Kaplan–Meier method, and the comparison between the two survival curves was tested using the log-rank test. The Kaplan–Meier method was selected due to its greater result accuracy for small groups and censored data and was used for generating 2-year survival percentages and graphs. The stratified log-rank test was used to assess group differences in OS. Hazard ratios and associated 95% confidence intervals (95% CI) were calculated with the use of a cox regression analysis. Time was calculated from the date of diagnosis to the event of interest, which was death due to any cause. Results are considered statistically significant when the P value is less than or equal to 0.05. Stratified cox regression analysis was used for subgroup analysis. This study has been reported in line with the STROCSS 2021 criteria²². This study has been registered in Research Registry with unique identifying number: researchregistry9050.

Results

During the study period, 175 NPC patients who were treated between 2016 and 2018 at the two hospitals were initially included in the study; 21 patients with early stage, 5 patients with subsequent lines of treatment, and 25 patients with missing data were excluded from the analysis, leaving a final sample size of a total of 124 patients included in the study. Eighty-one patients were in the IMW group, and 43 patients were in the non-IMW group (Fig. 1). Regarding the study’s baseline characteristics, 70% of the NPC patients included in the study were male. The median age of patients in the IMW group was slightly higher at 50 years compared to the non-IMW group at 46.5 years. The IMW group had a significantly higher percentage of patients with a WHO type 3 histopathology grade at 92.6% compared to the non-IMW group at 55.8% (P<0.01). Additionally, patients in the IMW group had a slightly better performance status, with 19.8% of patients having the ECOG performance status of 0, while none of the non-IMW group patients had a similar performance status (P<0.01) (Table 1).

Figure 1.

Study flow diagram. IMW, independent multidisciplinary work; NPC, nasopharyngeal cancer.

Table 1.

Baseline characteristics.

Characteristics	IMW (n=81)	Non-IMW (n=43)	Significance
Sex (n, %)
Male	57 (70.4)	31 (72.1)	0.84*
Female	24 (29.6)	12 (27.9)
Age	50 (15–76)	46.5 (16–73)	0.34†
Initial complaint (n, %)
Intracranial symptoms	11 (13.6)	11 (25.6)	0.06‡
Neck symptoms	36 (44.4)	16 (37.2)
Eye symptoms	3 (3.7)	7 (16.3)
Ear symptoms	11 (13.6)	3 (7.0)
Nose symptoms	15 (18.5)	6 (14.0)
Other	5 (6.2)	0
BMI	20.1 (13.3–32.3)	19.8 (13.0–28.3)	0.63†
ECOG (n, %)
0	16 (19.8)	-
1	46 (56.8)	21 (48.8)	<0.01‡
2	17 (21.0)	15 (34.9)
3	2 (2.5)	7 (16.3)
Comorbidity (n, %)
Yes	29 (35.8)	13 (30.2)	0.54*
No	52 (64.2)	30 (69.8)
WHO histopathology grade (n, %)
1–2	6 (7.4)	19 (44.2)	<0.01*
3	75 (92.6)	24 (55.8)
Cancer stage (n, %)
Locally advanced	20 (24.7)	13 (30.2)	0.51*
Advanced	61 (75.3)	30 (69.8)
Distant metastasis
Yes	54 (66.7)	19 (44.2)	0.01*
No	27 (33.3)	24 (55.8)
Treatment
Palliative	9 (11.1)	0 (0)	<0.01‡
Sequential CRT	69 (85.2)	33 (76.7)
Concurrent CRT	0 (0)	8 (18.6)
Chemotherapy only	3 (3.7)	0 (0)
Radiotherapy only	0 (0)	2 (4.7)

^*Chi-square test.

^†Mann–Whitney test.

^‡Kruskal–Wallis test.

BMI, body mass index; CRT, chemoradiotherapy; ECOG, Eastern Cooperative Oncology Group; IMW, independent multidisciplinary work.

There was a statistically significant difference in staging for both groups. In the IMW group, 75.3% were in the advanced stage, and 66.7% of patients were with distant metastasis, while in the non-IMW group, 69.8% were in the advanced stage, and 44.2% were with distant metastasis (P=0.01). For the treatment approach, there was a statistically significant different approach for both groups (P<0.01). However, most patients from both groups received sequential chemoradiotherapy (85.2% vs. 76.7% in IMW and non-IMW groups, respectively).

The IMW group had better overall survival (OS) rate compared to the non-IMW group in 1-year survival rate 66.7% versus 46.5%, respectively, with hazard ratio (HR)=0.7, 95% CI 0.49–0.99, P=0.03; and 2-year as well 40.7% versus 16.3%, respectively, with HR=0.4, 95% CI 0.19–0.83, P<0.01. After 36 months of follow-up, the median OS in the IMW group was not reached, while in the non-IMW group it was 12 months (95% CI, 8.78–15.22) with HR: 0.47 (95% CI, 0.28–0.78; P<0.01) using the log-rank test (Fig. 2). Using univariate survival analysis, IMW approach (P<0.01), ECOG performance status, and therapy approach (P<0.01) had been associated significantly with survival. Assuming that all the proportional hazard requirements are fulfilled, IMW approach, ECOG status, clinical stage, distant metastasis status, and treatment approach variables are included in multivariate analysis. From cox regression multivariate analysis, the IMW approach (HR: 0.43; 95% CI, 0.22–0.86; P=0.02), ECOG status, distant metastasis (HR: 1.92; 95% CI, 1.03–3.56; P=0.04), and treatment approach had significant association with survival outcome (Table 2).

Figure 2.

Kaplan–Meier survival curve. A protective factor for the survival of patients was shown by IMW group (HR=0.47; P<0.01). HR, hazard ratio; IMW, independent multidisciplinary work.

Table 2.

Cox regression univariate and multivariate survival analysis.

	Univariate analysis		Multivariate analysis
Variable	HR (95% CI)	P	HR (95% CI)	P
IMW
No	1		1
Yes	0.47 (0.28–0.78)	<0.01	0.43 (0.22–0.86)	0.02
Sex
Male	1
Female	1.09 (0.63–1.87)	0.54
ECOG
0	1		1
1	0.24 (0.12–0.49)	<0.01	0.20 (0.77–0.54)	<0.01
2	0.72 (0.36–1.46)	0.37	0.53 (0.19–1.42)	0.21
3	11.51 (3.94–33.57)	<0.01	8.56 (2.26–32.48)	<0.01
WHO histopathology
Grade 1–2	1
Grade 3	0.79 (0.43–1.43)	0.43
Clinical stage
Stage 3	1		1
Stage 4	1.76 (0.93–3.33)	0.07	1.59 (0.77–3.27)	0.21
Distant metastasis
No	1		1
Yes	1.5 (0.87–2.57)	0.56	1.92 (1.03–3.56)	0.04
Comorbidity
No	1
Yes	1.27 (0.74–2.18)	0.38
Treatment approach
Palliative therapy	1		1
Sequential CRT	0.31 (0.11–0.73)	0.04	0.24 (0.08–0.72)	0.01
Concurrent CRT	0.17 (0.81–0.35)	<0.01	0.27 (0.06–1.09)	0.07
Chemotherapy only	2.66 (0.55–12.97)	0.22	7.32 (0.98–55.98)	0.06
Radiotherapy only	0.09 (0.11–0.73)	0.02	0.42 (0.01–0.62)	0.02

CRT, chemoradiotherapy; ECOG, Eastern Cooperative Oncology Group; IMW, independent multidisciplinary work.

From a subgroup analysis of the hazard ratio stratified by the IMW approach (Fig. 3), overall, the IMW approach was found to significantly improve the survival in most variables. The maximum benefit of IMW was observed in patients who had distant metastasis (HR: 0.28; 95% CI, 0.15–0.57), ECOG performance status 1 (HR: 0.36; 95% CI, 0.14–0.91), WHO tumor grade 1–2 (HR: 0.10; 95% CI, 0.01–0.98), sequential CRT (HR: 0.37; 95% CI, 0.20–0.67), and clinical stage 4 (HR: 0.42; 95% CI, 0.24–0.74) compared to the other group. In patients with ECOG 3, the IMW approach did not show statistically significant improvement in survival.

Figure 3.

Overall survival in subgroups according to MDT approach. CRT, chemoradiotherapy; ECOG, Eastern Cooperative Oncology Group; IMW, independent multidisciplinary work.

Discussion

This study is the first in Indonesia to report a comparison between two hospitals regarding the implementation of an MDT-based approach in cancer treatment. Given the premise that the country has a high incidence of NPC with low survival⁴, the findings of the present study highlight the essentials of MDT practice. Cancer treatment is a complex process that requires specialized care, affordable facilities, and the interaction of various health services in different care settings (primary, secondary, and tertiary). It involves high costs and a combination of therapeutic modalities that are complementary to each other^8,12. The MDT approach has been successfully implemented in the treatment of other types of cancer and has been shown to improve patients’ quality of life, staging accuracy, selection of appropriate treatment, and treatment of other symptoms. Studies have also reported that MDT can increase patient satisfaction rates, reduce patient treatment time, and speed up the time to diagnosis^23–29.

Building an effective cancer MDT is somehow quite challenging. Every organization needs mutual cooperation to be effective. It is essential for a team with a diverse specialty background to effectively interact to keep everyone on the same page. To avoid any inconvenience and to maintain a simple and easy working environment, this can be accomplished by assigning roles to individuals and creating teams. In difficult cases, such as those with uncommon subtypes of the disease, failure of prior therapy, substantial comorbidities, or social or psychological issues, MDT working is most beneficial. In fact, evidence demonstrates that complicated cases result in higher-quality decision-making and more extensive discussion contributions from the participating MDT members³⁰. Regular team meetings should be held in an environment of cooperation, with minimal to no competition between the many specialties and ‘egos’, and a manager who is respected for his or her expertise, professionalism, and depths of wisdom and empathy³¹.

The core of the MDT approach is the unification of several scientific fields in patient management. This approach has been implemented in current treatment for head and neck conditions, especially for NPC. The management requires a different therapeutic approach due to the many variations in symptoms and side effects of treatment as well as patients’ physical and psychological aspects involved in the treatment. With a team consisting of personnel from various scientific backgrounds, MDT is expected to improve survival and patients’ quality of life¹⁰.

In this study, it was observed that the two hospitals involved had similar facilities and healthcare backgrounds, but they had different approaches to treating NPC patients, which resulted in different outcomes. The non-IMW group hospital had a high proportion of NPC patients managed independently by ENT specialists without much collaboration with medical oncologists and other specialists. This presented a potential opportunity for differences in management and outcomes between the MDT and non-MDT groups.

The results of the study showed that implementing IMW (Interdisciplinary Multidisciplinary Workgroup), which is an initial form of MDT (Multidisciplinary Team) in the management of NPC patients is correlated with a significant increase in survival rates despite the fact that the OS is still lower when compared to those in China with 5-year OS of 83.2%, and other developed countries^3–7. Although other aspects such as less advanced radiation treatment than those in developed countries might influence the whole patients’ survival, the implementation of IMW yet has brought more benefit to the local NPC cases. In this study, metastatic patients were more found in the IMW group setting, thus still having better survival outcomes compared to patients in the non-IMW group. Furthermore, this also shows that implementing MDT with members spanning across different disciplines, such as a medical oncologist, radiation oncologist, ENT specialist, pathologist, and other specialties, can facilitate good and mature discussion to determine the most appropriate treatment plan for patients. Each team member has their respective role and can complement each other. During MDT discussions, information about patients can be better collected and this will increase accuracy in decision-making. This study shows that the application of IMWs increases survival rates. Patients who received treatment with IMW indeed had better survival compared to those who did not receive a similar approach. These results are similar to studies conducted by Shang et al. in China, Anand et al. in India, and Friedland in the UK^32–36.

MDT meetings have been performed as part of cancer care services in Europe, the United States, and Australia. Most of the cancer centers in Indonesia do not commonly apply MDT meetings. MDT meetings are thus divided into two subgroups based on whether the MDT organization includes certain fundamental components. A well-organized MDT has a better infrastructure for meetings, as well as better meeting planning than a disorganized MDT. Interestingly, a disorganized MDT had a worse survival rate compared to non-MDT-treated patients³⁶. Some challenges in applying MDT in Indonesia are: lack of beneficial knowledge of the MDT, not included as a mandatory program in the national policy, sharing competencies between different oncology specialists leading to fragmented cancer care, and lack of spirit of collaboration.

Apart from IMW, distant metastasis status and treatment choice also affect the survival rate. Patients without distant metastasis had a higher 2-year survival rate compared to those with metastasis. In Indonesia, MDT is not a common approach used in cancer therapy. IMW is a simple and incomplete form of MDT that could be attempted during the study period. However, patients who were managed with this simple ‘MDT’ approach proved to have better outcomes, leading us to believe that a true MDT approach would have much better outcomes. The MDT is thus an essential part of cancer care in order to promote consistent and equitable delivery of the safe and high-quality care necessary to improve patient outcomes to all cancer patients. To improve the consistency and quality of cancer care in Indonesia, MDT should be incorporated into the national cancer care pathway.

The study has a few limitations, which include the retrospective nature of the study, which limited the number of patients included due to incomplete data. Propensity score matching was not used, which may have introduced bias into the study. Data on adverse events of chemotherapy or radiotherapy were not collected. Future studies with prospective designs are needed to determine the impact of the MDT approach on reducing therapeutic complications and length of stay, as well as improving the quality of life of patients.

Conclusion

This study found that stage 3 and 4 NPC patients are better treated with IMW approach and associated with a higher survival rate compared to those without IMW. We believe that MDT-based care has the potential to improve outcomes in cancer patients.

Ethical approval

Ethical approval for this study was given by the Ethical Committee of Dr. Kariadi General Hospital with Ethical Clearance Number 906/EC/KEPK-RSDK/2021.

Consent

Written informed consent was obtained from the patient for the publication of this study.

Sources of funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author’s contribution

D.R., V.Y., Y.R.P., and E.A.P.: contributed to study design; D.R., V.Y., Y.R.P., K.W.T.H., S.H.H., C.H., N.Y., and W.D.: contributed to data collection; D.R., V.Y., Y.R.P., and D.G.P.: contributed to data analysis; D.R., V.Y., Y.R.P., E.A.P., I.K., B.S., D.S., K.W.T.H., S.H.H., and I.P.: contributed to writing the paper.

Conflicts of interest disclosure

The authors declare that there are no conflicts of interest.

Research registration unique identifying number (UIN)

1. Research registry: not applicable.

2. Unique identifying number or registration ID: researchregistry9050.

3. Hyperlink to your specific registration (must be publicly accessible and will be checked): https://www.researchregistry.com/browse-theregistry# home/registrationdetails/64698e16a9d175002765174b/.

Guarantor

The guarantors of the study are D.R., V.Y., and Y.R.P.

Data availability statement

Data could be obtained by requesting it from the corresponding author via E-mail.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Assistance with the study

The authors thank C. Suharti, Mika. L. Tobing, Suyono, and Johan Kurnianda for their guidance and support in the manuscript preparation.

Presentation

None.